In the human world, olfaction serves to heighten or discriminate our aesthetic sense, while in other animals it is an important survival sense, upon which the well-being and sometimes the safety of the animal itself is dependent on. The partial or complete loss of smell (anosmia) affects approximately 2.5 million people in the United States and poses serious health risks as the presence of rancid food; toxic odors and smoke often go undetected. The clinical treatment of anosmia will require a better understanding of the mechanisms that regulate differentiation, proliferation and the injury response of the precursor, the multi-potent neuronal stem cells in the olfactory epithelium (OE). Olfactory receptor neurons (ORN) are the only mammalian neurons which undergo continuous neurogenesis through their life, suggesting that a neuronal stem cell exists in this system.
An aroma compound, also known as odorant, aroma, fragrance, flavor, is a chemical compound that has a smell or odor. A chemical compound has a smell or odor when two conditions are met: the compound needs to be volatile, so it can be transported to the olfactory system in the upper part of the nose, and it needs to be in a sufficiently high concentration to be able to interact with one or more of the olfactory receptors. Typically, odorants are small molecules in a range of 40 to 400 Daltons.
Aroma compounds can be found in food, wine, spices, perfumes, fragrance oils, and essential oils. For example, many aroma compounds form biochemically during ripening of fruits and other crops. In wines, most form as byproducts of fermentation. Odorants can also be added to a dangerous odorless substance, like natural gas, as a warning. Many of the aroma compounds also play a significant role in the production of flavorants, which are used in the food service industry to flavor, improve and increase the appeal of their products.
The olfactory mucosa is an organ made up of the olfactory epithelium and mucus. The mucus protects the olfactory epithelium and allows odors to dissolve so that they can be detected by olfactory receptor neurons. In mammals, the olfactory mucosa is located on the roof of the nasal cavity, above and behind the nostrils.
Cells in the olfactory mucosa have been shown to have a degree of plasticity. Because of this, these cells hold potential for therapeutic applications, have been used in clinical trials for adult stem cell therapeutic treatments, and have been successfully harvested for future applications.
The olfactory epithelium is a specialized epithelial tissue inside the nasal cavity that is involved in smell. In humans, the olfactory epithelium measures about 1 inch wide by 2 inches long (about 2 cm by 5 cm) and lies on the roof of the nasal cavity about 3 inches (about 7 cm) above and behind the nostrils. The olfactory epithelium is the part of the olfactory system directly responsible for detecting odors.
The tissue is made of three types of cells: the olfactory receptor neurons, which transduce the odor to electrical signals, the supporting cells, which protect the neurons and secrete mucus, and the basal cells, which are a type of stem cell that divide into olfactory receptor neurons to replace dead receptor neurons. The olfactory epithelium is divided into four zones from ventral to dorsal. Each olfactory receptor is expressed throughout one zone.
In mammals, odorants are inhaled through the nose where they contact the olfactory epithelium. Olfactory receptor neurons in the olfactory epithelium transduce molecular features of the odorants into electrical signals which then travel along the olfactory nerve into the olfactory bulb. Axons from the olfactory sensory neurons converge in the olfactory bulb to form tangles called glomeruli (singular glomerulus). Inside the glomulerus, the axons contact the dendrites of mitral cells and several other types of cells. Mitral cells send their axons to a number of brain areas, including the piriform cortex, the medial amygdala, and the entorhinal cortex. The piriform cortex is probably the area most closely associated with identifying the odor. The medial amygdala is involved in social functions such as mating and the recognition of animals of the same species. The entorhinal cortex is associated with memory. The exact functions of these higher areas are a matter of scientific research and debate.
Olfactory receptors belong to class A of the G protein-coupled receptor. In vertebrates, the olfactory receptors are located in the cilia of the olfactory sensory neurons. In insects, olfactory receptors are located on the antennae. Sperm cells also express odor receptors, which are thought to be involved in chemotaxis to find the egg cell.
It is believed that rather than binding to specific ligands like most receptors, olfactory receptors bind to structures on odor molecules. Once the odorant has bound to the odor receptor, the receptor undergoes structural changes and it binds and activates the olfactory-type G protein on the inside of the olfactory receptor neuron. The G protein (Golf and/or Gs) in turn activates the lyase adenylate cyclase, which converts ATP into cyclic AMP (cAMP). The cAMP opens ion channels that allow calcium and sodium ions to enter into the cell, depolarizing the olfactory receptor neuron and beginning an action potential which carries the information to the brain.
There are a wide range of different odor receptors, with as many as 1,000 in the mammalian genome. Olfactory receptors may make up as much as 3% of the genome. Only a portion of these potential genes form functional odor receptors. According to an analysis of the Human genome project, humans have 347 functional genes coded for olfactory receptors. The reason for the large number of different odor receptors is to provide a system for detecting as many different odors as possible. Even so, each odor receptor does not correspond to just one odor. Each individual odor receptor is broadly tuned to be activated by a number of similar structures. Like the immune system, this system allows molecules that have never been encountered before to be characterized. Also, most odors activate more than one type of odor receptor. This aspect provides for the identification of an almost limitless number of different molecules.
Damage to the olfactory system can occur for a number of different reasons. For example, damage to the olfactory system can occur by traumatic brain injury, cancer, inhalation of toxic fumes, or neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease. These conditions can cause anosmia (complete loss of ability to detect odors) or hyposmia (partial loss of the ability to detect odors). Even old age can cause anosmia or hyposmia; in fact most people suffer from some degree of hyposmia with aging.
The ability to smell is important not only to the survival of human beings, but is also an important aspect of a fulfilling life experience. The loss of smell can have a far reaching impact on a person's metal health and overall quality of life. Therefore, there is a continued need to develop techniques for maintaining, enhancing or improving the ability to smell odorants, especially for those people who exhibit anosmia. There is also a need to develop techniques for reducing the ability to smell an odorant or odorants, especially when the odorant or odorants are non-toxic but still unpleasant.